Chirality Effects on Peptide Self-Assembly Unraveled from Molecules to Materials

Abstract

Summary Self-assembling short peptides are attractive minimal systems for mimicking the constituents of living systems and building (bio)materials. The combination of both d- and l-amino acids into heterochiral sequences is a versatile strategy for building durable supramolecular architectures, especially when their homochiral analogs do not self-assemble. The reasons for this divergent behavior have remained obscure until now. Here, we elucidate how and why homochiral and heterochiral peptides behave differently. We identify a key spectroscopy signature and its corresponding molecular conformation, whereby an amphiphilic structure is uniquely enabled by the peptide stereochemistry. Importantly, we unravel the self-assembly process as a continuum from the conformation of single molecules to their organization into nano- and microstructures and through to macroscopic hydrogels, which are probed for cytotoxicity in fibroblast cell culture. In this way, (bio)material properties at the macro-scale can be linked to the chemical structure of their building blocks at the angstrom scale.